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Welsh Daffodils & Snowdrops - Herbal Flowers for Alzheimer’s & Poliomyelitis?
King Alfred Daffodil ,
(Narcissus Spps.) – Photo: John O’Neill, 2005 Floriade, Canberra On the first day of November some potentially advantageous news was announced for Alzheimer’s disease (AD) sufferers regarding the supply of galantamine, which is marketed as the drug Razadyne, (formerly Reminyl) and is used to slow the progress of AD. Galantamine is one of the drugs that NICE recently disallowed for use and distribution for ‘early stage Alzheimer’s’ in England and Wales because the compounds are too expensive to be put on the National Health list. Harnessing the power of the Daffodil, the Welsh national flower, a six month trial on seven sites in the Black Mountains, mid-Wales, is currently underway to ascertain whether daffodils can be farmed there to produce the compound galantamine, which has previously been collected from plants in the wild.1 All being well, the project offers a cheaper drug source. It could also be a useful means of diversification for farmers involved in its production. Galantamine, originally extracted from wild snowdrops in the Balkans, was subsequently produced by a synthetic process that is very expensive. According to lead researcher of the daffodil project, Professor Trevor Walker, 2 the aim of this research, if it is successful and it provides a properly monitored supply of galantamine, could give “a very good chance” to AD patients to be kept out of care-homes for a few years 3 and change the lives of thousands of people. It would also reduce the stress to patients’ families who also suffer greatly from the effects of pre-senile deterioration during the life of their loved ones. Together with farmers involved in the trials, opinion has it that the plants grown in Wales are particularly good at producing the compound. It was noticed there is a significant increase in the compound’s yield with altitude. It is not yet known whether this fortuitous result is due to altitude alone or with climate conditions combined.4 However, if the enterprise proves successful, which is basically replicating the growing conditions of the Balkans, with a view to developing selected strains of daffodils for this purpose, it could cut the drug’s price to about half the existing cost of production, 5 as well as assist the Welsh hill farmers to diversify in their otherwise difficult farming environment. The project gives Wordsworth’s lovely poem, The Daffodils, a whole new meaning and perhaps people would more truly appreciate “A host of golden daffodils … fluttering and dancing in the breeze.” Indeed to see: “Ten thousand [] at a glance, Tossing their heads in sprightly dance. … “ would be a wondrous sight for troubled minds just to know these common plants contain such a power for good. Curiously, one species of daffodil, (Narcissus obvallaris), is found only in a small area around Tenby, Pembrokeshire, Wales.6 The other gift of Nature to aid AD is the Snowdrop. From delving a little further into its past, it seems snowdrops or daffodils may be able to solve some other current health problems besetting our modern world.
Common Snowdrops (Galanthus nivalis L.) Photo: February 2004 on the South-East slopes of Mt. Kanin west of Bovec, East Julian Alps (Posocje, Slovenia) Copyright © 2004 Dr. Amadej Trnkoczy … these frail snowdrops that together cling, And nod their helmets, smitten by the wing Of many a furious whirl-blast sweeping by … (‘On Seeing a Tuft of Snowdrops in a Storm’ by William Wordsworth 1819) 7 Alzheimer’s disease (AD) takes the frail, complex and delicate brain by storm, and so it is fitting that the first plant that became a drug, ‘the snowdrop’, to come to the aid of this devastatingly debilitating disease should be a mixture of frailty and strength like the human brain. It is a delicate plant of hope, which when past the darkest days pushes up its fragile flowers with remarkable strength through often tough icy ground to signal winter’s nearly over every year. The Medical History of the Snowdrop The story of Galantamine8 for the treatment of Alzheimer’s disease in the West started with a species of snowdrop (Galanthus woronwii Los.) in eastern European Bulgaria. Historically, there seems to be no record of snowdrops growing wild in Britain before 1770, and the first garden reference is made to them in Gerard’s Herbal of 1597. It is thought that monks may have brought snowdrops to Britain from Italy in the 15th century, because the flowers are often found in the gardens of old monasteries. However, we cannot know for sure when snowdrops may have first been used for medicine, even if in old herbal books the snowdrop is not found. For example, the Celts’ pagan Druid priests, who travelled abroad to the East from the Mediterranean before settling West in Britain, were physicians. They treated with both herbs and potions, and performed surgery. The Druids’ presence in Britain also pre-dates the arrival of Christianity, monks and monasteries. Gaius Julius Caesar, the Roman Emperor (100BC-44BC) certainly knew quite a lot about the druid sects in Gaul (Caesar The Gallic War VI.13-14) and Christianity may have arrived sometime after the Roman conquest (43AD), but it probably did not take root in Britain until the Roman Emperor Constantine’s (272-337AD) Christianization of the Empire in the 4th –century AD. As each Celtic tribe had to maintain a hospital, which was staffed by the druids and their students, more discoveries may yet come to light.9 Certainly, there was a small hospital to care for sick pilgrims set up in Jerusalem 900 years ago which was run by monks from the local Benedictine Abbey.10 The Church was very rich and benefited from many gifts of property in Europe, as well as in the East. Eventually, this ‘order’ morphed into the autonomous new order of the Hospital of St John of Jerusalem (1113AD). The ‘Hospitallers’ had religious connections with Italy from whence snowdrops are said to have come to Britain; both brothers and sisters took vows of poverty, chastity and obedience, and their main aim was to care for the sick. They also dispersed throughout Europe and established hospitals to treat the sick and were the forerunners of our modern St. John’s Ambulance Brigade. It is perfectly possible that we just do not yet know all there is to be known about plants like ‘the snowdrop’, and if previously to modern discoveries they had a part to play in early medicine. By scientific estimation, it has been said, more archival and ethonpharmacuetical research is needed. So far, in accordance with what is known, it appears definite that the snowdrop (Galanthus spps.) and other Lilliaceae were not commonly used in European medicines until after WWII (1939-1945) in orthodox medicine.11 ‘According to unconfirmed reports, in the 1950s, a Bulgarian pharmacologist noticed the use of common snowdrop growing in the wild – people rubbed it on their foreheads to ease nerve pain.’ [Probably the leaves or the bulbs, as it is these and not the flowers that contain galantamine.] ‘British pharmacologist E. J. Shellard recalls a presentation in 1965 by a Russian pharmacognocist reporting about a peasant woman living at the foot of the Caucasian mountains who, when young children developed symptoms of an illness, which as he described them, was obviously poliomyelitis, gave them a decoction of the bulbs of the Caucasian snowdrop (G. woronwii Los.) and the children recovered without showing any signs of paralysis.’12 To give credit where it is due, the Russians, their satellite States and some of the Eastern Bloc countries behind the Iron Curtain were streets ahead in a wide spectrum of research matters during the Cold War. Most of the early investigations on galantamine were conducted in Communist Bulgaria (People’s Republic of Bulgaria) and the USSR during this period. In fact, the first free elections in Bulgaria since 1931 were held June 1990. Things have changed, nowadays foreigners, including the British, are buying holiday homes in beautiful Bulgaria. Whatever, in the early 1950s it was the Russian pharmacologist Mashkovsky who worked with galantamine isolated from the snowdrop (G. woronwii). A year later, Mashkovsky and Kruglikoca-Lvova, produced the first published work and demonstrated the AChE-inhibiting13A properties of the compound. In 1957 galantamine was isolated from the leaves of the common snowdrop (G. nivalis L.) and the first galanthamine drug ‘Nivalin’ was produced.13 As important as galantamine is to AD, it is from the past we learn how else it may help another difficult disease with devastating effects – Poliomyelitis. “Snowdrop and related species have now been used internally for 40 years for the reversal of neuromuscular blockade and for the treatment of neurological conditions such as post-polio paralysis and myasthenia gravis. When researchers demonstrated that galanthamine penetrated the blood-brain barrier, its effects on the Central Nervous System (CNS) became of interest.”14 Detailed researches only started in the 1980s. In 1986 ‘Shire’, a British company founded and funded in the UK by four entrepreneurs, acquired the rights to galantamine, as well as developing a partnership with Janssen to develop this product into ‘Reminyl’. From very early days, Shire concentrated on developing personal relationships with hospital doctors and specialists – a cornerstone in the company’s strategy that remains today. The rest as they say is history, or nearly 800 research papers’ worth of investigations, experiments, studies and validation for galantamine. Since 1951, galantamine has been used throughout Eastern Europe for the alleviation of neuromuscular ailments, such as neuritis and neuralgia. It also acts as a muscle stimulant and e.g. counteracts the effects of ‘curare’.15 Because of galantamine’s effect of enhancing neurotransmission in the brain, its primary use across Eastern Europe in the past half-century has been for the treatment of poliomyelitis. In retrospect, there is also the indication that peasant people had already been using snowdrop bulbs to treat children suffering from poliomyelitis who, importantly, recovered without any signs of paralysis.16 Although the snowdrop’s bulbs are used for AD, memory problems, trigeminal neuralgia, nerve pain, myasthenia and menses forcing, 17 it is its ability to aid poliomyelitis that might afford another appropriate use for it now. What is Poliomyelitis? Poliomyelitis, often called ‘polio’ or ‘infantile paralysis’ (Polio affects children under five years of age), is an ancient disease, it was first recognized as a medical entity by Jakob Heine 18A in 1840. In fact, the effects of a polio infection have been known since prehistory. Egyptian paintings and carvings depict otherwise healthy people with withered limbs, walking with canes at a young age &c. It is hypothesized that the Roman Emperor Claudius (10BC-54AD) was stricken with the disease as a child, which caused him to walk with a limp for the rest of his life.18 The malady is a virally induced infectious disease which spreads via the faecal-oral route. The virus enters the body through the mouth and multiplies in the intestine. It may proceed to the blood-stream and into the central nervous system causing muscle weakness and often paralysis in a matter of hours.19 Initial symptoms are fever, fatigue, headache, vomiting, stiffness in the neck and pain in the limbs. One in 200 infections leads to irreversible paralysis - usually in the legs. Among those paralysed, 5%-10% die when their breathing muscles become immobilized.20 There is no cure for polio, it can only be prevented. Polio vaccine, given multiple times, can protect a child for life.21 Polio cases have decreased by over 99% since 1988, from an estimated more than 350,000 cases in more than 125 endemic countries, to 1,951 reported cases in 2005 worldwide. In 2006, only four countries in the world remain endemic for the disease – the lowest number in history, which is the result of the global effort to eradicate the disease.22 Vaccination and eradication efforts led by the World Health Organization (WHO) and The Rotary Foundation of Rotary International are credited with the reduction of the number of annually diagnosed cases from the hundreds of thousands to around a thousand (plus).23 In 2002, the WHO announced that Europe is polio-free, 24 but that status quo might not continue with the vast numbers involved in the proliferation of migrants to the UK and other EU countries where the disease has been eradicated. Could Galantamine help Poliomyelitis in India? It has been reported, as recently as this month, that despite massive immunisation efforts, almost a third of all polio cases in the world occur in India.25 UK experts at Imperial College London have identified the main factors that let the virus rage there is poor sanitation and overcrowding.26 The latter is not something which in India with its spiralling population can be easily ‘wiped out’. Added to which, last year only 66 cases of polio were recoded in India, but there have been 522 cases so far this year!26 In a 2004, in a review by British Scientists on galanthamine for AD, it was stated: “Of note, little is known about the early history of the drug’s development. The review also points to other gaps in our knowledge about the enthopharmacology, pharmacology and clinical use of galanthamine.”27 Hopefully, this may be a helpful clue or ‘trigger’ to further investigations of galanthamine’s potential role to aid poliomyelitis sufferers. Lead researcher, Dr Nicholas Grassly, 28 in the latest research regarding India’s poliomyelitis plight, 29 has said that in the impoverished Indian states of Uttar Pradesh and Bihar, where India’s recent polio epidemics originate, poor sanitation and high population density are key obstacles to eradicating the virus; plus water or food contaminated by the faeces of infected people could pass the virus on to others. Overcrowding increases the risk the virus will spread, and high birth rates make it difficult to immunize new babies against polio in time.30 There are several problems about dealing with the situation. Until 2005, the vaccine used was designed to fight three strains of virus that cause polio, but individuals needed more doses of the vaccine to offer effective protection against the different strains.31 Some people did not receive enough doses, meaning polio could continue to thrive.32 The researchers believe that using a vaccine that targets the type 1 strain of polio virus, which is currently the dominant strain in India, with a monovalent vaccine32A might be the way to eradicate polio, as it offers protection much faster for fewer doses than the traditional trivalent vaccine.33 However, it is an outsized challenge, as 250,000 children are born every month that all need vaccinating and it only works if the children are vaccinated. Eradication is achievable only if a sufficient number of children are reached in time and quickly. Therefore, with galanthamine’s past credentials and its ability to aid children with polio, without showing any sign of paralysis, begs the question: might the scientific community find a degree of solution to the problem by employing galanthamine to aid the overseas poliomyelitis situation? This all may be a shot in the dark or pure speculation, but India is a vast continent with a variety of terrains. If suitable conditions can be found in a little country like England to grow daffodils to procure galanthamine, there is likely every chance that India could provide its own flower crops to supply galanthamine for dementia and poliomyelitis, e.g. possibly in conjunction with a UK-based biochemical company, to provide the drug at a realistic cost. Sadly, as things stand, dementia is largely a hidden problem in India and there is little awareness of it among the general community.34 Affected families tend not to seek help, despite the high levels of strain they experience. Qualitative research in Goa has shown that while clinic doctors tend not to see people with dementia, local community health workers were aware of many cases in the homes they visited.35 Although it is right that charity should begin at home when it comes to ‘early stage Alzheimer’s’ sufferers getting the drugs that may help them, at the same time we need to acknowledge that diseases from obesity to dementia have gone ‘global’. Even if considering national protection against the recurrence of poliomyelitis first and foremost, for it should be noted that migratory TB which was virtually eradicated in the UK is on the increase again, it would seem that further scientific investigation of galanthamine’s wider prowess, which encompasses poliomyelitis, is something that needs to be brought to the attention of the scientific community and further investigations could be made into this aspect of galanthamine deserves support. To bring the matter home, a recent Eurosurveillance peer-reviewed European information on communicable disease and control report regarding poliomyelitis concluded that: “Through impressive international and inter-agency collaboration, poliomyelitis has become a rare disease in the world. However, the proclaimed target, global eradication of wild type poliovirus has yet to be reached. 36 “An absence of cases over an extended period in a country or region may give a false impression that the disease is not longer a problem. Recent episodes in Africa and Asia remind us of the fragility of immune protection in many populations and that all European countries should evaluate polio immunisation coverage.37 “In addition, the PEI (Polio Eradication Initiative) can only succeed if sufficient resources are made available for immunisation campaigns and surveillance. The main supporters of the global programme, WHO, UNICEF, Rotary International, and the United States Centres for Disease Control and Prevention, would certainly welcome increased contributions from European countries.”38 It reads like a paean to the potential of daffodils’ and snowdrops’ galanthamine. References: 1. ‘Flower Trail for Alzheimer’s Drug’ – BBC News Online 1st November 2006. 2. Ibid. 3. Professor Trevor Walker, geneticist and biochemist, founder of ‘Alzheim’ based at the Great Barn Business Park in Talgarth, near Brecon, Powys, has a distinguished career in the development of plants for medicinal and other purposes. From Corporate Wales - http://64.233.183.104/search?q=cache:Jl-m5c5SCw0J:www.corporatewales.com/2006/08_Healthcare%26LifeSciences.pdf+Professor+Trevor+Walker+based+at&hl=en&gl=uk&ct=clnk&cd=1 4. ‘Flower Trail for Alzheimer’s Drug’ – BBC News Online 1st November 2006. 5. Ibid. 6. Daffodil:http://www.bbc.co.uk/wales/culture/sites/aboutwales/pages/culture.shtml 7. William Wordsworth: (April 1770-April 1850): A major English Romantic Poet who helped launch the Romantic Age in English literature. He was England’s Poet Laureate from 1883 until his death in 1850. This poem ‘On Seeing a Tuft of Snowdrops in a Storm’ was composed in one of the valleys of Westmoreland, Cumbria, UK. The complete poem:
“WHEN haughty expectations prostate lie; And grandeur crouches like a guilty thing, Oft shall the lowly weak, till nature bring Mature release, in fair society Survive, and Fortune’s utmost anger try; Like these frail snowdrop that together cling, And nod their helmets, smitten by the wing Of many a furious whirl-blast sweeping by. Observe the faithful flowers! If small to great May lead the thoughts, thus struggling used to stand The Emathian phalanx, nobly obstinate; And so the bright immortal Theban band, Whom onset, fiercely urged at Jove’s command, Might overwhelm, but could not separate. “
Emathian: An epithet given to Alexander the Great; the name comes form the district of Emathia which was sometimes synonymous with the whole of Makedon (Macedonia). Theban: of or relating to the Egyptian city of Thebes or its people or culture. Jove: In Roman mythology, Jupiter (sometimes shortened to Jove) held the same role as Zeus in the Green pantheon. He was called Jupiter Optimus Maximus (Jupiter best and Greatest) as the patron deity of the Roman state, in charge of laws and social order. 8. Galantamine (Galanthamine): belongs to a class of drugs called acteylcholinesterase inhibitors. Sold under the brand name Razadyne, formerly Reminyl, prevents the breakdown of acetycholine in the brain. 9. The Druids: http://www.angelfire.com/wi/THECELTS/druids.html ‘The Gundestrup Cauldron’: is a richly ornamented silver cauldron from the Raeve Bog at Gundestrup, Jutland, probably placed there in the 4th or 3rd-century BC. Now housed in the Danish National Museum in Copenhagen, acc. English Archaeologist, Timothy Taylor, in the American Scientific magazine intimately connects the Druids’ travels East to India and Hinduism and, therefore, knowledge imparted to the Celts by that part of the world. -http://www.celticgrounds.com/chapters/encyclopedia/g.html 10. St John, Cymru Wales ‘the first to care’ (Monks & Medicine): The Order of St John of Jerusalem, the St John Ambulance Association and the St. John Ambulance Brigade – http://www.celticgrounds.com/chapters/encyclopedia/g.html 11. Galantamine: Scientific progress and modern history. www.pjonline.com/pdf/xmas2004/pj_20041218_alzheimers.pdf 12. Ibid. Shellard E. J. ‘Alkaloids from Snowdrops,’ The Pharmaceutical Journal 2000:264-883. 13. Ibid. 13A. AChE - Acetylcholinesterase: An enzyme that degrades the neurotransmitter acetylcholine in the brain and other tissues of the body. Acetylcholine: a chemical substance that sends signals between nerve cells (called neurotransmission) and is therefore called a neurotransmitter. Neurotransmitters are secreted by neurons (nerve cells) into space between neurons called the synapse. Acetylcholine is a primary neurotransmitter in the brain, and is associated with memory and cognition. It is a neurotransmitter which plays an important role in memory. It is used for control of sensory input signals and muscular control. ACh is a stimulatory transmitter. When released by muscle nerves, it makes those muscles contract. It is made form the precursor nutrient ‘choline’ and there is some evidence that increased dietary choline can increase production and use of acetylcholine. Also, many drugs affect the production and release of this neurotransmitter. 14. Galantamine: Scientific progress and modern history. www.pjonline.com/pdf/xmas2004/pj_20041218_alzheimers.pdf 15. Curare (Chondrodendron tomentosum): is a large liana, or vine, found in the canopy of the S. American rainforest. It is known that some Indians of S. America crush and cook the roots and stems, and add other plants and venomous animals, mixing it until it becomes a light syrup. They call this mixture ‘ampi’, or ‘curaré’, which they use on the tip of their arrows and darts to hunt wild game. The name comes from the Indian word meaning ‘poison’. The active ingredient in ‘curaré’, D-tubocurarine, is used in medicine. - http://www.blueplanetbiomes.org/curare.htm 16. Snowdrops - http://www.bbc.co.uk/dna/h2g2/A3694728 17. Snowdrop (Galanthus nivalis) by Eva. – http://en.heilkraeuter.net/herbs/snowdrop.htm 18. Poliomyelitis: World Health Organization (WHO) - http://www.who.int/mediacentre/factsheets/fs114/en/ & http://en.wikipedia.org/wiki/Polio 18A. Jakob (or Jacob) Heine (1800-1879): was a German orthopaedist famous for his study, in 1840, into poliomyelitis, which was the first medical report on the disease, and the first time the illness was recognized as a clinical entity. Poliomyelitis is often known as the Heine-Medin disease, after the work of Heine and Karl Oskar Medin (1847-1927), a Swedish paediatrician. 19. Poliomyelitis: World Health Organization (WHO) - http://www.who.int/mediacentre/factsheets/fs114/en/ & http://en.wikipedia.org/wiki/Polio 20. Ibid. 21. Ibid. 22. Ibid. 23. Ibid. 24. Ibid. 25. Polio in India ‘can be wiped out’ – BBC News Online 16th November 2006. 26. Ibid. 27. ‘Galanthamine from snowdrop – the development of a modern drug against Alzheimer’s disease from local Caucasian knowledge.’ Henrich M, Lee Teoh H. Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, London, UK. J Ethnopharmacol. 2004 Jun; 92(2-3):147-62. 28. Dr. Nicholas Grassly: Royal Society University Research Fellow and head of the disease ecology research group in the Department of infectious Disease Epidemiology is interested in uncovering the biological, behavioural and environmental drivers of infectious diseases of humans through statistical and model based analysis of surveillance data. He has had active collaboration with UNAIDS, the WHO, US Centres for Disease Control, the UK Health Protection Agency, the International Trachoma Initiative and other members of the department. Until October 2004, he co-ordinated the UNAIDS/WHO Reference Group on ‘Estimates Modelling and Projection’ for HIV/AIDS (http://www.epiderm.org/ ). 29. Polio in India ‘can be wiped out’ – BBC News Online 16th November 2006 & Polio in India ‘can be wiped out’ – BBC News Online 16th November 2006. & ‘New Strategies for the Elimination of Polio from India.’ Grassly NC, Fraser C, et al. Dept. of Infectious Disease Epidemiology, Imperial College London, London UK. Science. 2006 Nov 17; 314(5802):1150-1153. 30. Polio in India ‘can be wiped out’ – BBC News Online 16th November 2006 31. Ibid. 32. Ibid. 32A. Monovalent: Containing only one kind of antibody. 33. ‘New Strategies for the Elimination of Polio from India.’ Grassly NC, Fraser C, et al. Dept. of Infectious Disease Epidemiology, Imperial College London, London UK. Science. 2006 Nov 17; 314(5802):1150-1153. 34. ‘Dementia, the hidden problem.’ - http://www.alz.co.uk/1066/research/intervention/casefinder.html 35. Ibid. 36. Eurosurveillance report – Vol. 11, Issue 3: Peer reviewed European information on communicable disease and control. - http://www.eurosurveillance.org/ew/2006/060309.asp References: 1. World Health Organization. Polio Eradication Initiative. (PEI, http://www.who.int/countries/eth/areas/immunization/pei/en/) 2. CDC, Resurgence of wild poliovirus type 1 transmission and consequences of importation – 21 countries 2002-2005. MMWR 2006;55:145-150. (http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5506a1.htm) 3. WHO. Resurgence of wild poliovirus type 1 transmission and effect of importation into polio-free countries, 2002-2005. Wkly Epid Rec 2006;81:63-68. 4. Kew OM, Sutter RW, de Gourville EM, Dowdle WR, Pallansch MA. Vaccine-derived polioviruses and the endgame strategy for global polio eradication. Annu Rev Microbiol 2005;59:587-635. 5. Oostvogel PM, van Wijngaarden JK, van der Avoort HG, Mulders MN, Conyn-van Spaendonck MA, Rumke HC, van Steenis G, van Loon AM. Poliomyelitis outbreak in an unvaccinated community in The Netherlands, 1992-93. Lancet 1994;344:665-670. 6. WHO. Polio Endemic Countries Hit All-Time Low of Four. Press release. 1 February 2006 (http://www.polioeradication.org/content/pressreleases/20060201press.asp) 37. Ibid. 38. Ibid. |
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